Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo.
Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo.
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体内兴奋性和抑制性受体利用不同的突触后和跨突触机制。
DOI：
10.7554/elife.59613
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发表时间：
2021-10-18
期刊：
影响因子：
7.7
通讯作者：
Tomita S
中科院分区：
文献类型：
--
作者：
Miyazaki T;Morimoto-Tomita M;Berthoux C;Konno K;Noam Y;Yamasaki T;Verhage M;Castillo PE;Watanabe M;Tomita S
突触后的嗜离子性神经递质受体介导神经递质结合后的快速突触传递。通过胞质、膜和分泌蛋白的突触后和跨突触机制已被提出在突触后定位神经递质受体。然而，在突触后维持神经递质受体的关键机制尚不清楚。在这项研究中，我们以细胞自主的方式切除了成年小鼠大脑中的兴奋性或抑制性神经元。出乎意料的是，我们发现兴奋性AMPA受体在兴奋性突触前末端消融后仍保持突触后密度。相比之下，抑制性GABAA受体需要抑制性突触前终末才能在突触后定位。与这一发现一致的是，神经素-3 α在兴奋性突触前的异位表达可以将GABAA受体招募到接触的突触后位点，而神经素-3 α是一种假定的与天然GABAA受体复合物的跨突触相互作用物。这些结果为成熟哺乳动物大脑中兴奋性和抑制性突触后受体的维持建立了不同的机制。
Ionotropic neurotransmitter receptors at postsynapses mediate fast synaptic transmission upon binding of the neurotransmitter. Post- and trans-synaptic mechanisms through cytosolic, membrane, and secreted proteins have been proposed to localize neurotransmitter receptors at postsynapses. However, it remains unknown which mechanism is crucial to maintain neurotransmitter receptors at postsynapses. In this study, we ablated excitatory or inhibitory neurons in adult mouse brains in a cell-autonomous manner. Unexpectedly, we found that excitatory AMPA receptors remain at the postsynaptic density upon ablation of excitatory presynaptic terminals. In contrast, inhibitory GABAA receptors required inhibitory presynaptic terminals for their postsynaptic localization. Consistent with this finding, ectopic expression at excitatory presynapses of neurexin-3 alpha, a putative trans-synaptic interactor with the native GABAA receptor complex, could recruit GABAA receptors to contacted postsynaptic sites. These results establish distinct mechanisms for the maintenance of excitatory and inhibitory postsynaptic receptors in the mature mammalian brain.
DOI：
10.1085/jgp.60.3.248
发表时间：
1972-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hartzell HC;Fambrough DM
通讯作者：
Fambrough DM